The unfolded protein response (UPR) is triggered by:
Unfolded protein response is evolutionarily conserved stress signaling program activated when concentration of unfolded polypeptides in ER lumen exceeds buffering capacity of BiP and other chaperones, threatening proteostasis. Under basal conditions, BiP binds lumenal domains of three ER transmembrane sensors keeping them inactive: IRE1 bifunctional kinase-endoribonuclease that upon dimerization autophosphorylates and splices XBP1 mRNA removing 26 nucleotide intron producing active transcription factor inducing chaperones, lipid synthesis and ERAD genes; PERK kinase that phosphorylates eIF2α a
Ref: Walter & Ron, Science 334: 2011, UPR Triggered by Misfolded Proteins.